Objective To investigate the inhibitory effects of dihydromyricetin on the proliferation and migration of gastric cancer BGC-823 cells and explore the molecular mechanisms. Methods BGC-823 cells in routine culture were treated with different concentrations of dihydromyricetin (0, 40, 60, 80, 100, and 120 μg/mL) for 24 h, and the changes in cell viability were detected using CCK-8 assay; colony forming assay and Transwell assay were performed to assess the changes in colony-forming and migration abilities of the cells, respectively. The levels of MMP-2 and MMP-9 in the treated cells were determined using ELISA, and Western blotting was used to detect the expressions of E-cadherin, N-cadherin, cyclin D1, cyclin E1, HSP70 and HMGB1 and the phosphorylation levels of Akt and Stat3. Results CCK-8 assay showed that dihydromyricetin treatment dose-dependently inhibited the viability of BGC-823 cells (P<0.05). Treatment with dihydromyricetin obviously suppressed the proliferation and migration of BGC-823 cells, significantly reduced the expression levels of cyclin D1, cyclin E1 and N-cadherin, enhanced E-cadherin expression, inhibited the phosphorylation of Akt and stat3, and downregulated HMGB1 expression in the cells. The results of ELISA demonstrated significantly lowered levels of MMP-2 and MMP-9 in dihydromyricetin-treated cells. Conclusion Dihydromyricetin inhibits the proliferation and migration of BGC-823 cells through suppressing the activation of Akt/stat3 signaling pathways and HMGB1 expression.